The Insulin Resistance and Atherosclerosis Study (IRAS) is a multicenter study of the relationship between insulin resistance and cardiovascular disease (CVD) and its risk factors in a tri-ethnic (African-American, Hispanic, and non-Hispanic white) population aged 40 to 69 years at baseline. The study population was selected to insure adequate numbers of participants within gender and glucose tolerance groups (normal, impaired glucose tolerance, and non-insulin dependent diabetes mellitus [NIDDM]). IRAS is the first large epidemiologic study to include detailed measurements of insulin sensitivity and secretion. During the first four years of funding the IRAS investigators successfully designed and implemented the first phase of the study--a cross-sectional evaluation of 1,626 participants. The current proposal requests an additional five years of funding for the prospective follow-up and reexamination of the IRAS cohort. The requested funding period consists of three phases. During the first phase (Y05 and Y06), the investigators propose to conduct two substudies. The first will address the measurement of insulin sensitivity in individuals with NIDDM. This study will evaluate four alternative techniques for measuring insulin sensitivity in 50 non-IRAS volunteers. The second substudy will examine methodologic issues in the measurement of obesity and body fat distribution in a tri-ethnic subgroup of 240 IRAS participants. In addition, all IRAS participants will be contacted annually for incident cardiovascular and other major health events. During the second phase, (Y07 and Y08), a follow-up examination of the IRAS cohort will be conducted with the goal of determining predictors of changes in insulin sensitivity, cardiovascular risk factors, measures of atherosclerosis development, and incident cardiovascular events. Additionally, throughout the first fours (Y05-08) a major effort will continue to be devoted to the analysis and reporting of the cross- sectional data from the first IRAS examination. The final phase (Y09) will include database closure and archival, and analysis and reporting of the longitudinal results.